The Health and Economic Burdens of Lymphatic Filariasis Prior to Mass Drug Administration Programs.

BACKGROUND: The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was launched in 2000 with the goal of eliminating lymphatic filariasis (LF) as a public health problem by 2020. Despite considerable progress, the current prevalence is around 60% of the 2000 figure, with the deadline looming a year away. Consequently, there is a continued need for investment in both the mass drug administration (MDA) and morbidity management programs, and this paper aims to demonstrate that need by estimating the health and economic burdens of LF prior to MDA programs starting in GPELF areas. METHODS: A previously developed model was used to estimate the numbers of individuals infected and individuals with symptomatic disease, along with the attributable number of disability-adjusted life years (DALYs). The economic burden was calculated by quantifying the costs incurred by the health-care system in managing clinical cases, the patients' out-of-pocket costs, and their productivity costs. RESULTS: Prior to the MDA program, approximately 129 million people were infected with LF, of which 43 million had clinical disease, corresponding to a DALY burden of 5.25 million. The average annual economic burden per chronic case was US $115, the majority of which resulted from productivity costs. The total economic burden of LF was estimated at US $5.8 billion annually. CONCLUSIONS: These results demonstrate the magnitude of the LF burden and highlight the continued need to support the GPELF. Patients with clinical disease bore the majority of the economic burden, but will not benefit much from the current MDA program, which is aimed at reducing transmission. This assessment further highlights the need to scale up morbidity management programs.

Rare-event sampling of epigenetic landscapes and phenotype transitions.

Stochastic simulation has been a powerful tool for studying the dynamics of gene regulatory networks, particularly in terms of understanding how cell-phenotype stability and fate-transitions are impacted by noisy gene expression. However, gene networks often have dynamics characterized by multiple attractors. Stochastic simulation is often inefficient for such systems, because most of the simulation time is spent waiting for rare, barrier-crossing events to occur. We present a rare-event simulation-based method for computing epigenetic landscapes and phenotype-transitions in metastable gene networks. Our computational pipeline was inspired by studies of metastability and barrier-crossing in protein folding, and provides an automated means of computing and visualizing essential stationary and dynamic information that is generally inaccessible to conventional simulation. Applied to a network model of pluripotency in Embryonic Stem Cells, our simulations revealed rare phenotypes and approximately Markovian transitions among phenotype-states, occurring with a broad range of timescales. The relative probabilities of phenotypes and the transition paths linking pluripotency and differentiation are sensitive to global kinetic parameters governing transcription factor-DNA binding kinetics. Our approach significantly expands the capability of stochastic simulation to investigate gene regulatory network dynamics, which may help guide rational cell reprogramming strategies. Our approach is also generalizable to other types of molecular networks and stochastic dynamics frameworks.

Investment Success in Public Health: An Analysis of the Cost-Effectiveness and Cost-Benefit of the Global Programme to Eliminate Lymphatic Filariasis.

Background: It has been estimated that $154 million per year will be required during 2015-2020 to continue the Global Programme to Eliminate Lymphatic Filariasis (GPELF). In light of this, it is important to understand the program's current value. Here, we evaluate the cost-effectiveness and cost-benefit of the preventive chemotherapy that was provided under the GPELF between 2000 and 2014. In addition, we also investigate the potential cost-effectiveness of hydrocele surgery. Methods: Our economic evaluation of preventive chemotherapy was based on previously published health and economic impact estimates (between 2000 and 2014). The delivery costs of treatment were estimated using a model developed by the World Health Organization. We also developed a model to investigate the number of disability-adjusted life years (DALYs) averted by a hydrocelectomy and identified the cost threshold under which it would be considered cost-effective. Results: The projected cost-effectiveness and cost-benefit of preventive chemotherapy were very promising, and this was robust over a wide range of costs and assumptions. When the economic value of the donated drugs was not included, the GPELF would be classed as highly cost-effective. We projected that a typical hydrocelectomy would be classed as highly cost-effective if the surgery cost less than $66 and cost-effective if less than $398 (based on the World Bank's cost-effectiveness thresholds for low income countries). Conclusions: Both the preventive chemotherapy and hydrocele surgeries provided under the GPELF are incredibly cost-effective and offer a very good investment in public health.

DNA-Binding Kinetics Determines the Mechanism of Noise-Induced Switching in Gene Networks.

Gene regulatory networks are multistable dynamical systems in which attractor states represent cell phenotypes. Spontaneous, noise-induced transitions between these states are thought to underlie critical cellular processes, including cell developmental fate decisions, phenotypic plasticity in fluctuating environments, and carcinogenesis. As such, there is increasing interest in the development of theoretical and computational approaches that can shed light on the dynamics of these stochastic state transitions in multistable gene networks. We applied a numerical rare-event sampling algorithm to study transition paths of spontaneous noise-induced switching for a ubiquitous gene regulatory network motif, the bistable toggle switch, in which two mutually repressive genes compete for dominant expression. We find that the method can efficiently uncover detailed switching mechanisms that involve fluctuations both in occupancies of DNA regulatory sites and copy numbers of protein products. In addition, we show that the rate parameters governing binding and unbinding of regulatory proteins to DNA strongly influence the switching mechanism. In a regime of slow DNA-binding/unbinding kinetics, spontaneous switching occurs relatively frequently and is driven primarily by fluctuations in DNA-site occupancies. In contrast, in a regime of fast DNA-binding/unbinding kinetics, switching occurs rarely and is driven by fluctuations in levels of expressed protein. Our results demonstrate how spontaneous cell phenotype transitions involve collective behavior of both regulatory proteins and DNA. Computational approaches capable of simulating dynamics over many system variables are thus well suited to exploring dynamic mechanisms in gene networks.

Role of hydrophobicity on self-assembly by peptide amphiphiles via molecular dynamics simulations.

Using a novel coarse-grained model, large-scale molecular dynamics simulations were performed to examine self-assembly of 800 peptide amphiphiles (sequence palmitoyl-V3A3E3). Under suitable physiological conditions, these molecules readily assemble into nanofibers leading to hydrogel construction as observed in experiments. Our simulations capture this spontaneous self-assembly process, including formation of secondary structure, to identify morphological transitions of distinctive nanostructures. As the hydrophobic interaction is increased, progression from open networks of secondary structures toward closed cylindrical nanostructures containing either ß-sheets or random coils are observed. Moreover, temperature effects are also determined to play an important role in regulating formation of secondary structures within those nanostructures. These understandings of the molecular interactions involved and the role of environmental factors on hydrogel formation provide useful insight for development of innovative smart biomaterials for biomedical applications.

A tail of two peptide amphiphiles: effect of conjugation with hydrophobic polymer on folding of peptide sequences.

Peptide amphiphiles (PA) offer the potential of incorporating biological function into synthetic materials for tissue engineering in regenerative medicine. These hybrid conjugates are known to undergo self-assembly starting from single molecules to nanofibers before turning into hydrogel scaffolds-such a process involves conformational changes in secondary structures of peptides. Therefore, insights on the ability of peptide amphiphiles to form secondary structure as single molecules are useful for understanding self-assembly behavior. We report here a molecular simulation study of peptide folding by two PA sequences, each contains an alkyl tail and short peptide segment. The alkyl tail is observed to play two opposing roles in modulating sequence-dependent folding kinetics and thermodynamics. On one hand, it restricts conformational freedom reducing the entropic cost of folding, which is thus promoted. On the other hand, it acts as an interaction site with nonpolar peptide residues, blocking the peptide from helix nucleation, which reduces folding.

The global burden of trichiasis in 2016.

BACKGROUND: Trichiasis is present when one or more eyelashes touches the eye. Uncorrected, it can cause blindness. Accurate estimates of numbers affected, and their geographical distribution, help guide resource allocation. METHODS: We obtained district-level trichiasis prevalence estimates in adults for 44 endemic and previously-endemic countries. We used (1) the most recent data for a district, if more than one estimate was available; (2) age- and sex-standardized corrections of historic estimates, where raw data were available; (3) historic estimates adjusted using a mean adjustment factor for districts where raw data were unavailable; and (4) expert assessment of available data for districts for which no prevalence estimates were available. FINDINGS: Internally age- and sex-standardized data represented 1,355 districts and contributed 662 thousand cases (95% confidence interval [CI] 324 thousand-1.1 million) to the global total. Age- and sex-standardized district-level prevalence estimates differed from raw estimates by a mean factor of 0.45 (range 0.03-2.28). Previously non- stratified estimates for 398 districts, adjusted by ×0.45, contributed a further 411 thousand cases (95% CI 283-557 thousand). Eight countries retained previous estimates, contributing 848 thousand cases (95% CI 225 thousand-1.7 million). New expert assessments in 14 countries contributed 862 thousand cases (95% CI 228 thousand-1.7 million). The global trichiasis burden in 2016 was 2.8 million cases (95% CI 1.1-5.2 million). INTERPRETATION: The 2016 estimate is lower than previous estimates, probably due to more and better data; scale-up of trichiasis management services; and reductions in incidence due to lower active trachoma prevalence.

Prevalence of trachoma in 13 Local Government Areas of Taraba State, Nigeria.

PURPOSE: The purpose of these surveys was to determine the prevalence of trachomatous inflammation-follicular (TF) in children aged 1-9 years and trichiasis prevalence in persons aged ≥15 years, in 13 Local Government Areas (LGAs) of Taraba State, Nigeria. METHODS: The surveys followed Global Trachoma Mapping Project (GTMP) protocols. Twenty-five households were selected from each of 25 clusters in each LGA, using two-stage cluster sampling providing probability of selection proportional to cluster size. Survey teams examined all the residents of selected households aged ≥1 year for the clinical signs TF, trachomatous inflammation-intense (TI) and trichiasis. RESULTS: The prevalence of TF in children aged 1-9 years in the 13 LGAs ranged from 0.0-5.0%; Ussa LGA had the highest prevalence of 5% (95%CI: 3.4-7.2). Trichiasis prevalence ranged from 0.0-0.8%; seven LGAs had trichiasis prevalences above the threshold for elimination. The backlog of trichiasis in the 13 LGAs (estimated combined population 1,959,375) was 3,185 people. There is need to perform surgery for at least 1,835 people to attain a trichiasis prevalence in each LGA of <0.2% in persons aged ≥15 years. In six of the 13 LGAs, 80% of households could access washing water within 1 km of the household, but only one LGA had >80% of households with access to improved latrines. CONCLUSION: One of 13 LGAs requires antibiotic mass drug administration for active trachoma. Community-based trichiasis surgery needs to be provided in seven LGAs. There is a need to increase household-level access to improved washing water and latrines across the State.

Prevalence of trachoma in the Afar Region of Ethiopia: results of seven population-based surveys from the Global Trachoma Mapping Project.

PURPOSE: Trachoma is to be eliminated as a public health problem by 2020. To help the process of planning interventions where needed, and to provide a baseline for later comparison, we set out to complete the map of trachoma in Afar, Ethiopia, by estimating trachoma prevalence in evaluation units (EUs) of grouped districts ("woredas"). METHODS: We conducted seven community-based surveys from August to October 2013, using standardised Global Trachoma Mapping Project (GTMP) survey methodologies. RESULTS: We enumerated 5065 households and 18,177 individuals in seven EUs covering 19 of Afar's 29 woredas; the other ten were not accessible. 16,905 individuals (93.0%) were examined, of whom 9410 (55.7%) were female. One EU incorporating four woredas (Telalak, Dalefage, Dewe, Hadele Ele) was shown to require full implementation of the SAFE strategy for three years before impact survey, with a trachomatous inflammation-follicular (TF) prevalence in 1-9-year-olds of 17.1% (95%CI 9.4-25.5), and a trichiasis prevalence in adults aged ≥15 years of 1.2% (95%CI 0.6-2.0). Five EUs, covering 13 woredas (Berahle, Aba'ala, Dupti, Kurri, Elidihare, Ayesayeta, Afamboo, Bure Mudaitu, Gewane, Amibara, Dulecho, Dalolo, and Konebo), had TF prevalences in children of 5-9.9% and need one round of azithromycin mass treatment and implementation of the F and E components of SAFE before re-survey; three of these EUs had trichiasis prevalences in adults ≥0.2%. The final EU (Mile, Ada'ar) had a sub-threshold TF prevalence and a trichiasis prevalence in adults just >0.2%. CONCLUSION: Trachoma is a public health problem in Afar, and implementation of the SAFE strategy is required.

Prevalence of trachoma in the area councils of the Federal Capital Territory, Nigeria: results of six population-based surveys.

PURPOSE: The World Health Organization's (WHO's) global trachoma elimination programme recommends mapping of trachoma at district level for planning of elimination activities in affected populations. This study aimed to provide data on trachoma prevalence for the Area Councils of Nigeria's Federal Capital Territory (FCT). METHODS: Using the Global Trachoma Mapping Project (GTMP) protocols, in March and April 2014, we conducted a population-based cross-sectional survey in each of the six Area Councils of FCT. Signs were defined based on the WHO simplified grading scheme. RESULTS: 98% to 100% of the targeted households were enrolled in each Area Council. The number of children aged 1-9 years examined per Area Council ranged from 867 to 1248. The number of persons aged ≥15 years examined ranged from 1302 to 1836. The age-adjusted prevalence of trachomatous inflammation-follicular in 1-9-year-olds was <5% in each Area Council. The age- and gender-adjusted prevalence of trichiasis in those aged ≥15 years ranged from 0.0% to 0.3%; two Area Councils (Gwagwalada and Kwali) had prevalences above the 0.2% elimination threshold. The proportion of households with access to improved latrines and water sources ranged from 17 to 90% and 39 to 85% respectively. CONCLUSIONS: Gwagwalada and Kwali Area Councils need to perform more trichiasis surgeries to attain the trichiasis elimination prevalence target of 0.2% in persons aged ≥15 years. No Area Council requires mass antibiotic administration for the purposes of trachoma's elimination as a public health problem. All Area Councils need to accelerate provision of access to improved water sources and latrine facilities, to achieve universal coverage.

Quality Assurance and Quality Control in the Global Trachoma Mapping Project.

In collaboration with the health ministries that we serve and other partners, we set out to complete the multiple-country Global Trachoma Mapping Project. To maximize the accuracy and reliability of its outputs, we needed in-built, practical mechanisms for quality assurance and quality control. This article describes how those mechanisms were created and deployed. Using expert opinion, computer simulation, working groups, field trials, progressively accumulated in-project experience, and external evaluations, we developed 1) criteria for where and where not to undertake population-based prevalence surveys for trachoma; 2) three iterations of a standardized training and certification system for field teams; 3) a customized Android phone-based data collection app; 4) comprehensive support systems; and 5) a secure end-to-end pipeline for data upload, storage, cleaning by objective data managers, analysis, health ministry review and approval, and online display. We are now supporting peer-reviewed publication. Our experience shows that it is possible to quality control and quality assure prevalence surveys in such a way as to maximize comparability of prevalence estimates between countries and permit high-speed, high-fidelity data processing and storage, while protecting the interests of health ministries.

Trachoma in Viet Nam: results of 11 surveillance surveys conducted with the Global Trachoma Mapping Project.

PURPOSE: Following interventions against trachoma in Viet Nam, impact surveys conducted in 2003-2011 suggested that trachoma was no longer a public health problem. In 2014, we undertook surveillance surveys to estimate prevalence of trachomatous inflammation-follicular (TF) and trichiasis. METHODS: A population-based prevalence survey was undertaken in 11 evaluation units (EUs) encompassing 24 districts, using Global Trachoma Mapping Project methods. A two-stage cluster sampling design was used in each EU, whereby 20 clusters and 60 children per cluster were sampled. Consenting eligible participants (children aged 1-9 years and adults aged ≥50 years) were examined for trachoma. RESULTS: A total of 9391 households were surveyed, and 20,185 participants (98.8% of those enumerated) were examined for trachoma. EU-level TF prevalence in 1-9-year-olds ranged from 0% to 1.6%. In one cluster (in Hà Giang Province), the percentage of children with TF was 10.3%. The overall pattern of cluster-level percentages of children with TF, however, was consistent with an exponential distribution, which would be consistent with trachoma disappearing. Among people aged ≥50 years, prevalence of trichiasis by EU ranged from 0% to 0.75%; these estimates are equivalent to 0-0.13% in all ages. The prevalence of trichiasis unknown to the health system among people aged ≥50 years, by EU, ranged from 0% to 0.17%, which is equivalent to 0-0.03% in all ages. CONCLUSION: Findings suggest that trachoma is no longer a public health problem in any of the 11 EUs surveyed. However, given the high proportion of children with TF in one cluster in Hà Giang Province, further investigations will be undertaken.

Markov State Models of gene regulatory networks.

BACKGROUND: Gene regulatory networks with dynamics characterized by multiple stable states underlie cell fate-decisions. Quantitative models that can link molecular-level knowledge of gene regulation to a global understanding of network dynamics have the potential to guide cell-reprogramming strategies. Networks are often modeled by the stochastic Chemical Master Equation, but methods for systematic identification of key properties of the global dynamics are currently lacking. RESULTS: The method identifies the number, phenotypes, and lifetimes of long-lived states for a set of common gene regulatory network models. Application of transition path theory to the constructed Markov State Model decomposes global dynamics into a set of dominant transition paths and associated relative probabilities for stochastic state-switching. CONCLUSIONS: In this proof-of-concept study, we found that the Markov State Model provides a general framework for analyzing and visualizing stochastic multistability and state-transitions in gene networks. Our results suggest that this framework-adopted from the field of atomistic Molecular Dynamics-can be a useful tool for quantitative Systems Biology at the network scale.

Integrated Mapping of Yaws and Trachoma in the Five Northern-Most Provinces of Vanuatu.

Yaws and trachoma are targeted for eradication and elimination as public health problems. In trachoma-endemic populations mass administration of azithromycin can simultaneously treat yaws. We conducted a population-based prevalence survey in the five northernmost provinces of Vanuatu, where trachoma and yaws are suspected to be co-endemic. Clinical signs of trachoma were evaluated using the WHO simplified grading system, and skin examination with a serological rapid diagnostic test used to identify yaws. We enrolled 1004 households in 59 villages over 16 islands, and examined 3650 individuals of all ages for trachoma. The overall adjusted prevalence of trachomatous inflammation-follicular (TF) in 1-9 year-olds was 12.0% (95% Confidence Interval: 8.1-16.7%), and the overall adjusted prevalence of TT in those aged 15 years and greater was 0.04% (95% CI 0-0.14%). In multivariate analysis, the odds of children having TF was 2.6 (95% CI = 1.5-4.4) times higher in households with unimproved latrines, and independently associated with the number of children in the household (OR 1.3, 95% CI = 1.0-1.6 for each additional child). We examined the skin of 821 children aged 5-14 years. Two children had yaws, giving an estimated prevalence of active yaws in those aged 5-14 years of 0.2% (95% CI = 0.03-0.9%). Mass treatment with azithromycin is recommended in these provinces. Given the apparent low burden of yaws, integration of yaws and trachoma control programmes is likely to be useful and cost-effective to national programmes.

Application of a household-based molecular xenomonitoring strategy to evaluate the lymphatic filariasis elimination program in Tamil Nadu, India.

BACKGROUND: The monitoring and evaluation of lymphatic filariasis (LF) has largely relied on the detection of antigenemia and antibodies in human populations. Molecular xenomonitoring (MX), the detection of parasite DNA/RNA in mosquitoes, may be an effective complementary method, particularly for detecting signals in low-level prevalence areas where Culex is the primary mosquito vector. This paper investigated the application of a household-based sampling method for MX in Tamil Nadu, India. METHODS: MX surveys were conducted in 2010 in two evaluation units (EUs): 1) a hotspot area, defined as sites with community microfilaria prevalence ≥1%, and 2) a larger area that also encompassed the hotspots. Households were systematically selected using a sampling interval proportional to the number of households in the EU. Mosquito pools were collected and analyzed by real-time polymerase chain reaction (qPCR). Two independent samples were taken in each EU to assess reproducibility of results. Follow-up surveys were conducted in 2012. RESULTS: In 2010, the proportion of positive pools in the hotspot EU was 49.3% compared to 23.4% in the overall EU. In 2012, pool positivity was significantly reduced to 24.3% and 6.5%, respectively (p<0.0001). Pool positivity based on independent samples taken from each EU in 2010 and 2012 were not significantly different except for the hotspot EU in 2012 (p = 0.009). The estimated prevalence of infection in mosquitoes, measured by PoolScreen, declined from 2.2-2.7% in 2010 to 0.6-1.2% in 2012 in the hotspot area and from 0.9-1.1% to 0.2-0.3% in the larger area. CONCLUSIONS: The household-based sampling strategy for MX led to mostly reproducible results and supported the observed LF infection trends found in humans. MX has the potential to be a cost-effective, non-invasive monitoring and evaluation tool with sensitive detection of infection signals in low prevalence settings. Further investigation and application of this sampling strategy for MX are recommended to support its adoption as a standardized method for global LF elimination programs.

Prevalence of Trachoma in Kano State, Nigeria: Results of 44 Local Government Area-Level Surveys.

PURPOSE: We sought to determine the prevalence of trachoma in 44 Local Government Areas (LGAs) of Kano State, Nigeria. METHODS: A population-based prevalence survey was conducted in each Kano LGA. We used a two-stage systematic and quasi-random sampling strategy to select 25 households from each of 25 clusters in each LGA. All consenting household residents aged 1 year and above were examined for trachomatous inflammation-follicular (TF), trachomatous inflammation-intense (TI) and trichiasis. RESULTS: State-wide crude prevalence of TF in persons aged 1-9 years was 3.4% (95% CI 3.3-3.5%), and of trichiasis in those aged ≥15 years was 2.3% (95% CI 2.1-2.4%). LGA-level age- and sex-adjusted trichiasis prevalence in those aged ≥15 years ranged from 0.1% to 2.9%. All but 4 (9%) of 44 LGAs had trichiasis prevalences in adults above the elimination threshold of 0.2%. State-wide prevalence of trichiasis in adult women was significantly higher than in adult men (2.6% vs 1.8%; OR = 1.5, 95% CI 1.3-1.7; p = 0.001). Four of 44 LGAs had TF prevalences in 1-9-year-olds between 10 and 15%, while another six LGAs had TF prevalences between 5 and 9.9%. In 37 LGAs, >80% of households had access to water within 30 minutes round-trip, but household latrine access was >80% in only 19 LGAs. CONCLUSION: Trichiasis is a public health problem in most LGAs in Kano. Surgeons need to be trained and deployed to provide community-based trichiasis surgery, with emphasis on delivery of such services to women. Antibiotics, facial cleanliness and environmental improvement are needed in 10 LGAs.

Partnering for impact: Integrated transmission assessment surveys for lymphatic filariasis, soil transmitted helminths and malaria in Haiti.

BACKGROUND: Since 2001, Haiti's National Program for the Elimination of Lymphatic Filariasis (NPELF) has worked to reduce the transmission of lymphatic filariasis (LF) through annual mass drug administration (MDA) with diethylcarbamazine and albendazole. The NPELF reached full national coverage with MDA for LF in 2012, and by 2014, a total of 14 evaluation units (48 communes) had met WHO eligibility criteria to conduct LF transmission assessment surveys (TAS) to determine whether prevalence had been reduced to below a threshold, such that transmission is assumed to be no longer sustainable. Haiti is also endemic for malaria and many communities suffer a high burden of soil transmitted helminths (STH). Heeding the call from WHO for integration of neglected tropical diseases (NTD) activities, Haiti's NPELF worked with the national malaria control program (NMCP) and with partners to develop an integrated TAS (LF-STH-malaria) to include assessments for malaria and STH. METHODOLOGY/PRINCIPLE FINDINGS: The aim of this study was to evaluate the feasibility of using TAS surveys for LF as a platform to collect information about STH and malaria. Between November 2014 and June 2015, TAS were conducted in 14 evaluation units (EUs) including 1 TAS (LF-only), 1 TAS-STH-malaria, and 12 TAS-malaria, with a total of 16,655 children tested for LF, 14,795 tested for malaria, and 298 tested for STH. In all, 12 of the 14 EUs passed the LF TAS, allowing the program to stop MDA for LF in 44 communes. The EU where children were also tested for STH will require annual school-based treatment with albendazole to maintain reduced STH levels. Finally, only 12 of 14,795 children tested positive for malaria by RDT in 38 communes. CONCLUSIONS/SIGNIFICANCE: Haiti's 2014-2015 Integrated TAS surveys provide evidence of the feasibility of using the LF TAS as a platform for integration of assessments for STH and or malaria.

The health and economic benefits of the global programme to eliminate lymphatic filariasis (2000-2014).

BACKGROUND: Lymphatic filariasis (LF), also known as elephantiasis, is a neglected tropical disease (NTD) targeted for elimination through a Global Programme to Eliminate LF (GPELF). Between 2000 and 2014, the GPELF has delivered 5.6 billion treatments to over 763 million people. Updating the estimated health and economic benefits of this significant achievement is important in justifying the resources and investment needed for eliminating LF. METHOD: We combined previously established models to estimate the number of clinical manifestations and disability-adjusted life years (DALYs) averted from three benefit cohorts (those protected from acquiring infection, those with subclinical morbidity prevented from progressing and those with clinical disease alleviated). The economic savings associated with this disease prevention was then analysed in the context of prevented medical expenses incurred by LF clinical patients, potential income loss through lost-labour, and prevented costs to the health system to care for affected individuals. The indirect cost estimates were calculated using the human capital approach. A combination of four wage sources was used to estimate the fair market value of time for an agricultural worker with LF infection (to ensure a conservative estimate, the lowest wage value was used). RESULTS: We projected that due to the first 15 years of the GPELF 36 million clinical cases and 175 (116-250) million DALYs will potentially be averted. It was estimated that due to this notable health impact, US$100.5 billion will potentially be saved over the lifetimes of the benefit cohorts. This total amount results from summing the medical expenses incurred by LF patients (US$3 billion), potential income loss (US$94 billion), and costs to the health system (US$3.5 billion) that were projected to be prevented. The results were subjected to sensitivity analysis and were most sensitive to the assumed percentage of work hours lost for those suffering from chronic disease (changing the total economic benefit between US$69.30-150.7 billion). CONCLUSIONS: Despite the limitations of any such analysis, this study identifies substantial health and economic benefits that have resulted from the first 15 years of the GPELF, and it highlights the value and importance of continued investment in the GPELF.

Mapping Trachoma in the Solomon Islands: Results of Three Baseline Population-Based Prevalence Surveys Conducted with the Global Trachoma Mapping Project.

PURPOSE: We sought to complete the baseline trachoma map of the Solomon Islands by establishing prevalences of active trachoma and trichiasis in the provinces of Choiseul, Western, Rennell-Bellona, and Temotu. METHODS: Using the standardized methodology developed for the Global Trachoma Mapping Project, we conducted cross-sectional community-based surveys from September to November 2013. Choiseul and Western provinces were each mapped as separate evaluation units (EUs); Rennell-Bellona and Temotu were combined to form a third EU. RESULTS: A total of 9819 individuals were sampled for inclusion, with 9224 (93.3%) consenting to examination, of whom 4587 (46.3%) were female. Survey teams visited 82 villages, and surveyed 2448 households. Two EUs had prevalences of trachomatous inflammation - follicular (TF) in 1-9-year-olds over the 10% threshold at which WHO recommends mass distribution of azithromycin for at least 3 years (Western 20.4%, 95% confidence interval, CI 15.6-26.3%; Rennell-Bellona/Temotu 22.0%, 95% CI 18.5-26.0%). Choiseul had a TF prevalence of 6.1% (95% CI 4.1-8.6%), and met the criterion for a single round of mass antibiotic distribution before re-survey. The adjusted prevalences of trichiasis in those aged 15+ years were 0.0% (95% CI 0.0-0.2%) in Choiseul, 0.16% (95% CI 0.0-0.5%) in Western, and 0.10% (95% CI 0-0.3%) in Rennell-Bellona/Temotu provinces. All three EUs require implementation of the facial cleanliness and environmental improvement components of the trachoma elimination strategy. CONCLUSION: Active trachoma is prevalent in the Solomon Islands. However, there is little evidence of the blinding complications of trachoma being a public health problem there. Further research into the explanation for this phenomenon is warranted.

The Prevalence of Trachoma in Tigray Region, Northern Ethiopia: Results of 11 Population-Based Prevalence Surveys Completed as Part of the Global Trachoma Mapping Project.

PURPOSE: We aimed to estimate the prevalence of trachoma in each district ("woreda") of Tigray Region, Ethiopia. METHODS: We conducted 11 cross-sectional community-based surveys in evaluation units covering 34 rural woredas from January to March 2013 using the standardized methodology developed for the Global Trachoma Mapping Project. RESULTS: Teams visited 8034 households in 275 villages. A total of 28,581 consenting individuals were examined, 16,163 (56.7%) of whom were female. The region-wide adjusted trichiasis prevalence was 1.7% in those aged 15 years and older. All evaluation units mapped had a trichiasis prevalence over the World Health Organization elimination threshold of 0.2% in people aged 15 years and older. The region-wide adjusted prevalence of the clinical sign trachomatous inflammation - follicular (TF) in children aged 1-9 years was 26.1%. A total 10 evaluation units, covering 31 woredas, with a combined rural population of 4.3 million inhabitants, had a prevalence of TF ≥10%, and require full implementation of the SAFE strategy (surgery, antibiotics, facial cleanliness, and environmental improvement) for at least 3 years before impact surveys are undertaken. Of these, four evaluation units, covering 12 woredas, with a combined rural population of 1.7 million inhabitants, had a TF prevalence ≥30%. CONCLUSION: Both active trachoma and trichiasis are public health problems in Tigray, which needs urgent implementation of the full SAFE strategy.